摘要:

AbstractThe effects of spray‐dried yogurt powder product (YPP), bifidobacteria, and Lactobacillus acidophilus were studied during the initiation and promotion phases of carcinogenesis using the 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced mouse mammary carcinogenesis model. In two separate studies, Sencar mice were fed a diet consisting of 86%, 43%, or 0% YPP or 0% YPP, but with added cultures of bifidobacteria or L. acidophilus. When the animals were 55–63 days old, DMBA was administered by intragastric gavage at 1 mglmouse and continued once a week for six weeks. During the initiation study, the test diets were fed for four weeks before and during DMBA administration. One week after the final DMBA treatment, all animals were switched to a basal diet based on the AIN‐76 formulation. For the promotion study, the diets were introduced one week after the final dose of DMBA and fed for the remainder of the study. Palpable tumor development was monitored weekly throughout the studies. For the initiation study, mice fed 86%, 43%, or 0% YPP or 0% YPP supplemented with bifidobacteria or L. acidophilus had a histologically verified mammary tumor incidence of 15%, 35%, 19%, 30%, and 20%, respectively. The histologically verified tumor incidence for the promotion study was 48%, 58%, 36%, 59%, and 43% in the mice fed diets consisting of 86%, 43%, or 0% YPP or 0% YPP supplemented with bifidobacteria or L. acidophilus, respectively. The data indicate that neither the initiation nor the promotion phase of carcinogenesis is significantly affected by diets composed of 86% YPP, 43% YPP, 0% YPP, or 0% YPP supplemented with bifidobacteria or L. acidophilus.

ISSN:0163-5581    

DOI:10.1080/01635589509514398

出版商:Taylor&Francis Group    

年代:1995

数据来源: Taylor

摘要:

AbstractPoly(ADP‐ribose) is synthesized on nuclear proteins in response to DNA damage and plays an important role in DNA repair. Niacin and tryptophan are dietary precursors to NAD+, which is the substrate for poly(ADP‐ribose) synthesis. This study examined the influence of niacin status onpoly(ADP‐ribose) metabolism and carcinogenesis. Diets devoid of added niacin, with different levels of tryptophan, were used to produce moderate and severe niacin deficiencies in male Fischer‐344 rats. Control rats were pair fed niacin‐replete diets. After a 21‐day feeding period, rats were injected with diethylnitrosamine (DEN) (Expt 1, 200 mg/kg ip; Expt 2, 100 mg/kg ip). In Experiment 1, blood and liver NAD+and liver poly (ADP‐ribose) were measured over the next 15 hours. Whereas blood and liver NAD+were decreased by niacin deficiency, blood NAD+was not affected by DEN. Liver NAD+decreased significantly in response to DEN treatment in the pair‐fed groups, but it did not change in the niacin‐deficient groups. Unexpectedly, at 10 hours postinjection, liver poly (ADP‐ribose) accumulation was greater (p<0.05) in the niacin‐deficient than in the pair‐fed rats (n = 9), despite lower initial NAD* levels and a lack of NAD+disappearance in niacin‐deficient livers. In Experiment 2, livers were examined for the presence of altered hepatic foci three months after DEN exposure. There were no significant differences in the percentage of liver occupied by foci between the niacin‐deficient and pair‐fed groups (n = 8). These results indicate that niacin‐deficient rats were able to accumulate higher concentrations of hepatic poly(ADP‐ribose) in response to DEN and did not show elevated susceptibility to initiation of altered hepatic foci.

ISSN:0163-5581    

DOI:10.1080/01635589509514399

出版商:Taylor&Francis Group    

年代:1995

数据来源: Taylor

摘要:

AbstractThis study reports the modulating effect of some dairy products on initiation of putative preneoplasic lesions in rat colon (aberrant crypts) by 1,2‐dimethylhydrazine dihydrochloride. Uninoculated skim milk, skim milk fermented with Bifidobacterium sp Bio (Danone strain 173010), and a suspension of the same lactic acid bacteria were incorporated in the animals’diet. The tested diets significantly reduced the incidence of aberrant crypts compared with the control diet by 51%, 49%, and 61%, respectively.The effects of the diets on cecal pH, hepatic UDP‐glucuronyltransferase activity, and cecal microflora enzymeβ‐glucuronidase were also studied. There was no significant difference in cecal pH between rats fed experimental diets and control rat. The diet supplemented with the Bifidobacterium strain suspension significantly decreased only the cecalβ‐glucuronidase activity. Both enzyme activities were reduced in rats fed fermented skim milk‐or uninoculated skim milk‐supplemented diets compared with control animals.

ISSN:0163-5581    

DOI:10.1080/01635589509514400

出版商:Taylor&Francis Group    

年代:1995

数据来源: Taylor

摘要:

AbstractMammary tumor incidence, natural killer (NK) cell activity, and tumor necrosis factor‐α(TNF‐α) activity were measured in iron (Fe)‐deficient and iron‐replete rats treated with the carcinogen 7,12‐dimethylbenz[a]anthracene (DMBA). Female weanling rats were fed AIN‐76 diets: the iron‐deficient group was fed 5 mg Felkg diet; the control group was fed 50 mg Felkg diet; the food‐restricted group was fed 50 mg Felkg diet in the amount consumed by the iron‐deficient group; and the replete group was fed 5 mg Felkg diet for 45 days and then 50 mg Felkg diet. After six weeks of feeding, the rats were given a single intragastric dose of DMBA. Feeding the iron‐deficient diet for 20 weeks reduced hematocrit, hemoglobin, liver iron, and tumor iron values and increased spleen weight. Dietary iron repletion for 14 weeks reversed these effects of iron deficiency. Splenic NK cell cytotoxicity against YAC‐1 cells was highest in the control group. Repleting rats with 50 mg Felkg diet corrected iron deficiency but did not restore NK cell cytotoxicity. No significant differences in macrophage TNF‐αbioactivity were found among groups. Cumulative tumor incidence over all weeks was lowest in the iron‐deficient rats. Iron repletion during the promotion phase of tumorigenesis attenuates the protective effects of iron deficiency. Food restriction to the extent present in the iron‐deficient group did not protect against tumorigenesis. The iron‐deficient group had the lowest tumor burden and delayed onset of tumors. Iron deficiency significantly reduces tumor incidence in DMBA‐treated rats by mechanisms other than NK cell cytotoxicity, TNF‐a activity, and food restriction.

ISSN:0163-5581    

DOI:10.1080/01635589509514401

出版商:Taylor&Francis Group    

年代:1995

数据来源: Taylor

摘要:

AbstractThe influence of dietary caffeine on the genotoxicity of the cooked food mutagen 2‐amino‐3,8‐dimethylimidazo[4,5‐f]‐quinoxaline (MelQx) was evaluated using the host‐mediated assay in mice. For four weeks, BALBIc mice were fed a purified diet with or without caffeine (0.01% wt/wt in the diet). In the host‐mediated assay, Salmonella typhimurium TA98 was given intravenously immediately before an oral dose of MelQx (1.5 mglkg body wt). After one hour, the mice were killed, the Salmonellae were recovered from the liver, and the number of mutants (his+revertants) were determined. Consumption of caffeine led to a 47% reduction in the number of mutants induced by MelQx (p<0.001). Subsequent in vitro experiments using S. typhimurium TA98 revealed that the capacity of hepatic S‐9 fractions from the caffeine‐fed mice to covert MelQx to an active mutagen was reduced by approximately 35%. This effect was not attributable to caffeine in the S‐9 preparation. These data suggest that consumption of caffeine modifies MelQx mutagenicity by altering the spectrum of enzymes involved in its activation.

ISSN:0163-5581    

DOI:10.1080/01635589509514402

出版商:Taylor&Francis Group    

年代:1995

数据来源: Taylor

摘要:

AbstractFatty acid composition of triglycerides (TGs) and phospholipids (PLs) in breast adipose tissue was analyzed in 73 female breast cancer patients and 55 patients with benign breast disease. No differences were observed in the dietary intake of the major fatty acids (i.e., palmitic, stearic, oleic, and linoleic acids) or in the proportion of TGs and PLs in breast adipose tissue between the two groups. In postmenopausal women, however, the dietary intake ofeicosapentaenoic acid (20: 5n‐3) and docosahexaenoic acid (22: 6n‐3) was significantly lower in the breast cancer patients than in patients with benign breast disease. Accordingly, the percentage of docosahexaenoic acid of PLs in breast adipose tissue was significantly lower in breast cancer patients than in patients with benign breast disease among postmenopausal women. The stage of the breast cancer did not contribute to the observed alterations of fatty acid composition of PLs. Consonant with the previous epidemiologic data, the present results suggest that intake of the long‐chain n‐3 fatty acids (mainly derived from fish) may have a protective effect against breast cancer, particularly in postmenopausal women.

ISSN:0163-5581    

DOI:10.1080/01635589509514403

出版商:Taylor&Francis Group    

年代:1995

数据来源: Taylor

摘要:

AbstractThe RRR‐α‐tocopheryl succinate derivative of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of three metastatic human prostatic cancer cell lines, LNCaP, PC‐3, and DU‐145. LNCaP is a lymph node‐derived androgen‐sensitive prostate cell line; these cells are defective for response to transforming growth factor‐β(TGF‐β) but are normal for cell cycle‐related tumor suppressor genes: p53 and retinoblastoma (Rb). PC‐3 is a bone marrow‐derived androgen‐insensitive prostate cell line; these cells are defective for both p53 alleles but normal for both Rb alleles. DU‐145 is a brain‐derived androgen‐insensitive prostate cell line; these cells are defective for both p53 and both Rb alleles. VES at 5, 10, and 20μg/ml inhibited DNA synthesis in the three cell lines in a dose‐dependent manner. Purified TGF‐β1at 1 ng/ml inhibited DNA synthesis of PC‐3 cells within 24–72 hours and DU‐145 cells at 72 hours but did not inhibit DNA synthesis of LNCaP cells. Previous studies in our laboratory showed that VES growth‐inhibited tumor cells secrete biologically active antiproliferative factor TGF‐βs, suggesting that VES's mechanism of growth inhibition may involve the TGF‐βsystem of growth control. The significance of the studies reported here is that VES can inhibit the proliferation of 1) cells that have lost the ability to respond to TGF‐βs (i.e., LNCaP), 2) cells that are defective for Rb and p53 (i.e., DU‐145), and 3) cells that are defective for p53 (i.e., PC‐3), critical cell cycle regulatory molecules. Taken together, these studies show that VES most likely inhibits the proliferation of tumor cells via mechanism(s) in addition to and independent of TGF‐β, as well as the functional status of Rb and p53.

ISSN:0163-5581    

DOI:10.1080/01635589509514404

出版商:Taylor&Francis Group    

年代:1995

数据来源: Taylor

摘要:

AbstractThe RRR‐α‐tocopheryl succinate form of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of avian reticuloendotheliosis virus‐transformed RECC‐UTC4–1 (C4–1) lymphoblastoid cells in a dose‐dependent manner in vitro. Analyses of conditioned medium (CM) from VES growth‐inhibited cells revealed a potent antiproliferative activity. Characterization of the antiproliferative activity as transforming growth factor‐β(TGF‐β) was established by 1) growth inhibition of TGF‐β‐responsive Mv1Lu mink lung and murine CTLL‐2 cell lines, 2) a combination of physical characteristics including heat stability, acid stability, and Bio‐Gel P‐60 column chromatography elution profile, 3) neutralization of the antiproliferative activity by antibodies specific for TGF‐β, and 4) immunoprecipitation of metabolically labeled TGF‐βin CM from VES‐treated C4–1 cells by use of TGF‐β‐specific antibodies. Northern blot analyses of total cellular RNA revealed that VES does not alter the levels of constitutively expressed TGF‐βisoform‐specific mRNAs; namely, VES does not alter the levels of the 3.9‐and 4.1‐kb TGF‐β2mRNAs, the 3.0‐kb TGF‐β3mRNA, or the 2.5‐, 2.7‐, and 1.7‐kb TGF‐β4mRNAs. The data show that VES inhibits C4–1 cell proliferation and induces the cells to produce and secrete active forms of TGF‐β, suggesting that one mechanism whereby VES inhibits C4–1 cell proliferation may be via the TGF‐βpathway for cellular growth control.

ISSN:0163-5581    

DOI:10.1080/01635589509514405

出版商:Taylor&Francis Group    

年代:1995

数据来源: Taylor

摘要:

AbstractOmega‐3 fatty acids, which are contained in fish oils and certain vegetable oils in contrast to corn oil or safflower oil rich in omega‐6 fatty acids (linoteic acid), have been reported to reduce the carcinogenesis in several organs. In this study, the modifying effect of menhaden fish oil was investigated on the occurrence of azoxymethane (AOM)‐induced glutathione S‐transferase placental form (GST‐P) positive hepatocellular foci, recognized preneoplastic lesions in the liver, in male F344 rats. Starting at five weeks of age, groups of animals were fed ad libitum a semipurified diet containing 5% corn oil (low fat). At seven weeks of age, all animals except the vehicle‐treated groups were injected subcutaneously with AOM (15 mglkg body wt, 1×lwk for 2 wks). Four days after the second injection, groups of animals were fed the diets containing 4% menhaden oil + 1% corn oil (low fish oil diet), 22.5% menhaden oil + 1% corn oil (high fish oil diet), and 5% corn oil. Thirty‐four weeks after AOM injections, all animals were necropsied. Livers were sectioned and performed immunohistochemical staining of GST‐P for quantitative analysis of enzyme altered foci of the liver. The results demonstrate that the density and the unit area of AOM‐induced enzyme altered foci in the liver were significantly lower in the high fish oil group (0.60±0.08/cm2, 3.0±0.4×10−4) than in the 5% corn oil group (2.71±0.33/cm2, 16.6±2.6×10−4) and the low fish oil group (1.66±0.33/cm2, 11.1±1.9×10−4). The denisty and the unit area of foci in the low fish oil group were lower than in the 5% com oil group, without statistical difference. The size of foci was also reduced in the high fish oil group, but the significant relationship could not be observed among the groups. These results indicate that fish oil rich in highly polyunsaturated omega‐3 fatty acids could modulate the occurrence of AOM‐induced GST‐P positive foci in rats.

ISSN:0163-5581    

DOI:10.1080/01635589509514406

出版商:Taylor&Francis Group    

年代:1995

数据来源: Taylor

摘要:

AbstractThe blue‐green microalgae Spirulina, used in daily diets of natives in Africa and America, have been found to be a rich natural source of proteins, carotenoids, and other micronutrients. Experimental studies in animal models have demonstrated an inhibitory effect of Spirulina algae on oral carcinogenesis. Studies among preschool children in India have demonstrated Spirulina fusiformis (SF) to be an effective source of dietary vitamin A. We evaluated the chemopreventive activity of SF (1 g/day for 12 mos) in reversing oral leukoplakia in pan tobacco chewers in Kerala, India. Complete regression of lesions was observed in 20 of 44 (45%) evaluable subjects supplemented with SF, as opposed to 3 of 43 (7%) in the placebo arm (p<0.0001). When stratified by type of leukoplakia, the response was more pronounced in homogeneous lesions: complete regression was seen in 16 of 28 (57%) subjects with homogeneous leukoplakia, 2 of 8 with erythroplakia, 2 of 4 with verrucous leukoplakia, and 0 of 4 with ulcerated and nodular lesions. Within one year of discontinuing supplements, 9 of 20 (45%) complete responders with SF developed recurrent lesions. Supplementation with SF did not result in increased serum concentration of retinol orβ‐carotene, nor was it associated with toxicity. This is the first human study evaluating the chemopreventive potential of SF. More studies in different settings and different populations are needed for further evaluation.

ISSN:0163-5581    

DOI:10.1080/01635589509514407

出版商:Taylor&Francis Group    

年代:1995

数据来源: Taylor